Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Clinical Research Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Biochim Biophys Acta Mol Cell Res. 2017 Jul;1864(7):1260-1273. doi: 10.1016/j.bbamcr.2017.03.006. Epub 2017 Mar 22.
Mitochondrial homeostasis is critical for keeping functional heart in response to metabolic or environmental stresses. Mitochondrial fission and fusion (mitochondrial dynamics) play essential roles in maintaining mitochondrial homeostasis, defects in mitochondrial dynamics lead to cardiac diseases such as ischemia-reperfusion injury (IRI), heart failure and diabetic cardiomyopathy. Mitochondrial dynamics is determined by mitochondrial fission and fusion proteins, including OPA1, mitofusins and Drp1. These proteins are tightly regulated by a series of signaling pathways through different aspects such as transcription, post translation modifications (PTMs) and proteasome-dependent protein degradation. By modulating these mitochondrial fission and fusion proteins, mitochondria fine-tune their metabolic status to meet the energy demands of the heart. Moreover, these mitochondrial fission and fusion proteins are essential for mediating mitochondrial autophagy (mitophagy), leading to clearance of damaged mitochondria to maintain a healthy population of mitochondria in heart under stressed conditions. Mitochondrial dynamics dependent improvement in mitochondrial metabolism and quality could partially reverse the pathological conditions of heart. This review describes an overview of mechanisms on mitochondrial dynamics regulation and provides potential therapeutic targets for treating cardiovascular diseases.
线粒体动态平衡对于维持心脏在代谢或环境应激下的正常功能至关重要。线粒体的分裂和融合（线粒体动力学）在维持线粒体动态平衡中起着重要作用，线粒体动力学的缺陷会导致心脏疾病，如缺血再灌注损伤（IRI）、心力衰竭和糖尿病心肌病。线粒体动力学由线粒体分裂和融合蛋白决定，包括 OPA1、融合蛋白和 Drp1。这些蛋白质通过一系列信号通路进行紧密调节，通过转录、翻译后修饰（PTMs）和蛋白酶体依赖的蛋白降解等不同方面进行调节。通过调节这些线粒体分裂和融合蛋白，线粒体可以微调其代谢状态，以满足心脏的能量需求。此外，这些线粒体分裂和融合蛋白对于介导线粒体自噬（mitophagy）至关重要，导致清除受损的线粒体，以维持心脏在应激条件下健康的线粒体群体。线粒体动力学依赖性的改善线粒体代谢和质量可以部分逆转心脏的病理状态。本综述描述了线粒体动力学调节的机制概述，并为治疗心血管疾病提供了潜在的治疗靶点。
